Characterization of the Barrier Properties of the Human Nail

Bibliographic Details
Main Author:	Smith, Kelly
Language:	English
Published:	University of Cincinnati / OhioLINK 2010
Subjects:	Pharmaceuticals Human Nail Plate Transungual Iontophoresis Ionic Strength pH Organic Solvent Effects
Online Access:	http://rave.ohiolink.edu/etdc/view?acc_num=ucin1289237023

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spelling	ndltd-OhioLink-oai-etd.ohiolink.edu-ucin12892370232021-08-03T06:14:20Z Characterization of the Barrier Properties of the Human Nail Smith, Kelly Pharmaceuticals Human Nail Plate Transungual Iontophoresis Ionic Strength pH Organic Solvent Effects <p>Topical therapies for the treatment of nail diseases are preferable. They reduce the likelihood of adverse effects associated with systemic medications and increase patient compliance. Due to the imperviousness of nail, however, topical delivery is challenging. The nail selects for the penetration of small, hydrophilic molecules. Most pharmaceutical agents are large and highly lipophilic, and are therefore unable to diffuse across the nail at therapeutic concentrations. Iontophoresis has been proposed as a mechanism to overcome the nail barrier to concurrently deliver and load the nail with drug. To optimize a transungual iontophoretic drug system, the transport barrier properties of the human nail plate during iontophoresis were characterized. Specifically, the effects of ionic strength, pH, and organic solvents on the barrier properties of nail were assessed in vitro through nail hydration/gravimetric, uptake, and transport studies. </p> <p>Permselectivity towards tetraethylammonium ion (TEA) was inversely related to ionic strength in both passive and iontophoretic transport. The permeability and transference number of TEA were higher at lower ionic strengths under symmetric conditions due to increased partitioning of TEA into the nail. Transference numbers were lower under asymmetric conditions compared with their symmetric counterparts. Nail hydration was independent of ionic strength and pH under moderate pH conditions and increased significantly under extreme pH conditions (pH >11). Likewise, nail permeability for water was pH-independent at pH 1 to 10 and an order of magnitude higher at pH 13. The results of passive and iontophoretic transport of Na and Cl ions are consistent with the published permselective properties of nail. Interestingly, extremely acidic conditions (e.g., pH = 1) altered nail permselectivity with the changes lasting several days at the higher pH conditions. Hydronium and hydroxide ion competition to iontophoretic transport was generally negligible at pH 3–11 but ion competition was significant at the extreme pH values studied. Nail uptake and permeability increased with increases in the organic solvent concentration for ethanol (EtOH), propylene glycol (PPG), and polyethylene glycol-400 (PEG). These changes coincided with differences in the solution viscosity as well as with changes in the barrier properties of the nail of which hydration was the most likely explanation. The more pronounced results for PPG and PEG as compared with those for EtOH are likely due to the differences in the viscosity and molecular size of the different organic solvents. </p> <p>There are four main practical implications from these results. First, the results suggest that positively charged drugs can effectively partition into the nail at low donor concentration due to ion-to-nail charge interactions. Second, the pretreatment of nail with solutions of extremely acidic pH (pH <3) or the pre-treatment/co-treatment of nail with extremely alkaline pH (pH >11) may be useful for enhancing transungual permeability. Third, the results suggest that pH modulations – between pH 3 and 11 – necessary to increase drug solubility will not affect drug transport. Fourth, these results suggest that increased drug solubility brought about by the use of organic solvents may be counteracted by increased nail barrier resistivity.</p> 2010 English text University of Cincinnati / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ucin1289237023 http://rave.ohiolink.edu/etdc/view?acc_num=ucin1289237023 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection	NDLTD
language	English
sources	NDLTD
topic	Pharmaceuticals Human Nail Plate Transungual Iontophoresis Ionic Strength pH Organic Solvent Effects
spellingShingle	Pharmaceuticals Human Nail Plate Transungual Iontophoresis Ionic Strength pH Organic Solvent Effects Smith, Kelly Characterization of the Barrier Properties of the Human Nail
author	Smith, Kelly
author_facet	Smith, Kelly
author_sort	Smith, Kelly
title	Characterization of the Barrier Properties of the Human Nail
title_short	Characterization of the Barrier Properties of the Human Nail
title_full	Characterization of the Barrier Properties of the Human Nail
title_fullStr	Characterization of the Barrier Properties of the Human Nail
title_full_unstemmed	Characterization of the Barrier Properties of the Human Nail
title_sort	characterization of the barrier properties of the human nail
publisher	University of Cincinnati / OhioLINK
publishDate	2010
url	http://rave.ohiolink.edu/etdc/view?acc_num=ucin1289237023
work_keys_str_mv	AT smithkelly characterizationofthebarrierpropertiesofthehumannail
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Characterization of the Barrier Properties of the Human Nail

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